The disulfide-metabolizing enzymes, glutathione insulin transhydrogenase and protein disulfide isomerase, are present in leukocytes. In the proposed research the enzymes will be extracted from rabbit leukocytes, purified using ion-exchange and gel filtration chromatography and their properties studied. The cellular localization of the activites in the leukocyte will be examined and their release from the cell in response to stimuli such as phagocytosis and endotoxin investigated. A possible pathophysiological role of the enzymes in rheumatoid arthritis will be examined in the following way: D-penticillamine and cetain anti-inflammatory drugs such as indomethacin used in the treatment of the disease will be examined for effects on the enzymes. The rationale for these experiments is that a sulfhydryl-disulfide interchange reaction catalyzed by the leukocyte enzymes using immunoglobulin as a substrate is important in the pathophysiology of rheumatoid arthritis. The ability of the enzymes to catalyze aggregation of IgG will be tested directly. Presumably, native IgG is not a substrate for the disulfide-metabolizing enzymes. Consequently, cleavage of its disulfide bonds by the enzymes will be investigated in the presence of certain animal and microbial products and after limited proteolysis of the protein.